The complex relationship between the host and its gut microbiota is shaped by a diverse array of reciprocal interactions, many of which are as of yet uncharacterized. While the gut microflora provides numerous benefits to the host, it has also been implicated in disease; dysbiosis of the gut microbiome is associated with inflammatory bowel disease and diet driven-shifts in microbial diversity can give rise to communities that exert a pathological effect on the host. Moreover, the gut microbiome is implicated in the development of metabolic syndrome. The goal of this project is to exploit the extreme phenotype of the arctic ground squirrel (Urocytellus parryii) to discover interrelationships between host physiology and the gut microbial community and to identify members of the gut microbiota which may influence, or be influenced by, host physiological condition and diet. The research design utilizes captive born arctic ground squirrels monitored for aspects of physiology (growth, adiposity, gut development). Dynamics of diversity of the gut microbiome will be assessed using data generated by pyrosequencing of microbial 16S rRNA genes and TRFLPs analysis; flow cytometry will be used to enumerate the community and short-chain fatty acid analysis will reveal functional changes in the microbiome. Host physiology will be compared across the summer active season and correlated to measured changes in the microbiome. The specific aims test the hypothesis that the gut microbial community is modulated in response to developmental changes in host physiology, and alteration of gut microbial diversity, abundance and activity will impact host physiology. Specific aim 1 will correlate physiological changes of th host with the development of the gut microbial community in juvenile arctic ground squirrels from weaning to 12-weeks post-weaning, with particular attention paid to the pre-hibernation fattening phase. By modulating the gut microbiome through the introduction of antibiotics at various time-points in development preceding hibernation, specific aim 2 will describe the influence of the gut microbiota on host physiology. Diet manipulations will be conducted to disentangle the influence of adiposity and diet of the host on microbial diversity such that specific aim 3 will independently quantify the effects of diet on host physiology and gut microbial diversity, activity and abundance in adult squirrels during the active season. The arctic ground squirrel naturally undergoes a brief season of extreme fat deposition during its annual cycle that provide an excellent platform upon which to investigate interrelationships between gut microbiota and obesity; therefore, our studies will contribute to the understanding of the complex interactions between the gut microbial community and development of obesity in humans . PUBLIC HEALTH RELEVANCE: The gut microbial community plays an important role in development, such as gut structure and function, and pathologies such as inflammatory bowel disease and obesity. Our experiments are designed to characterize the gut microbiota of the arctic ground squirrel, an animal that naturally pushes the known limits of mammalian physiology, with the goal of understanding the relationship between the gut microflora and host physiology. In particular, the arctic ground squirrel annually undergoes a discrete period of profound fattening in preparation for hibernation that provides an excellent platform upon which to investigate interrelationships between gut microbiota and obesity; therefore, our studies will contribute to the understanding of the complex interactions between the gut microbial community and human disease.